LHX2, LDB1, and EBF1 bind Olfactory Receptor gene and intergenic olfactory enhancers

Stable Identifier
Reaction [binding]
Homo sapiens
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Transcription factors LHX2 and EBF1 and scaffold protein LDB1 bind enhancers located between olfactory receptor (OR) genes (inferred from mouse homologs). OR genes are initially heterochromatic during development of the olfactory sensory neuron (OSN) lineage (McClintock et al. 2020). A few OR genes become weakly active and then one of these genes becomes highly active while all other OR genes are repressed by heterochromatin. In this way each OSN expresses only one OR gene. The single expressed OR gene is activated by a suprachromosomal cluster of intergenic olfactory enhancers located on the same chromosome and on other chromosomes (inferred from mouse homologs). Three dimension analysis of chromatin indicates 8-12 intergenic enhancers are sufficient to activate an OR gene (inferred from mouse homologs). Each intergenic olfactory enhancer is bound by the transcription factors LHX2 and EBF1 and by the scaffold protein LDB1, which may mediate enhancer-enhancer interactions (inferred from mouse homologs). As the expressed OR protein accumulates in the endoplasmic reticulum membrane, it activates the unfolded protein response, which increases translation of ADCY3 that then downregulates KDM1A (LSD) histone methyltransferase. The downregulation of KDM1A prevents any other OR genes from becoming active.

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